Thomas Lionel, Bellmont Sandrine, Christen Marie-Odile, La Roche Benoît, Monassier Laurent
Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, INSERM EMI 333, Faculté de Médecine, Université Louis Pasteur, 11 rue Humann, 67000 Strasbourg, France.
Fundam Clin Pharmacol. 2004 Dec;18(6):649-55. doi: 10.1111/j.1472-8206.2004.00282.x.
Adriamycin (ADR) is a widely used drug for the treatments of cancers. This study evaluates the effects of moxonidine and metoprolol on cardiac hemodynamics and survival in ADR-induced left ventricular dysfunction (total dose of 20 mg/kg in a 4-week regimen). Rats were treated with the centrally acting I(1)R agonist sympatho-inhibitor, moxonidine, or with the non-selective beta-adrenergic antagonist, metoprolol, during 1 month or until death. Treatments began 1 week after the onset of the ADR administration. Low doses (0.5 and 1 mg/kg/day) of moxonidine and metoprolol (10 mg/kg/day) improved cardiovascular function. High doses of moxonidine (3 mg/kg/day) and metoprolol (150 mg/kg/day) were cardiodepressive. Moxonidine and metoprolol both failed to improve survival. These data indicate that a treatment with these sympatho-inhibitors can reduce the left ventricular dysfunction induced by ADR. Moreover, these cardioprotective effects where obtained even when ADR was used at a dose regimen usually employed for its antineoplastic effects in rodents. Nevertheless, in this particular cardiomyopathy, we did not find any association between improvements of functional parameters and survival whatever the drug and the dose used. This problem points out the difficulty to prevent, at least with sympatho-inhibitory drugs alone, the mortality linked to the chronic cardiotoxicity of ADR.
阿霉素（ADR）是一种广泛用于治疗癌症的药物。本研究评估了莫索尼定和美托洛尔对阿霉素诱导的左心室功能障碍（4周方案中总剂量为20mg/kg）的心脏血流动力学和生存率的影响。在1个月内或直至死亡期间，用中枢作用的I(1)R激动剂交感神经抑制剂莫索尼定或非选择性β-肾上腺素能拮抗剂美托洛尔对大鼠进行治疗。治疗在阿霉素给药开始1周后开始。低剂量（0.5和1mg/kg/天）的莫索尼定和美托洛尔（10mg/kg/天）改善了心血管功能。高剂量的莫索尼定（3mg/kg/天）和美托洛尔（150mg/kg/天）具有心脏抑制作用。莫索尼定和美托洛尔均未能提高生存率。这些数据表明，用这些交感神经抑制剂治疗可减轻阿霉素诱导的左心室功能障碍。此外，即使以通常用于其在啮齿动物中的抗肿瘤作用的剂量方案使用阿霉素，也能获得这些心脏保护作用。然而，在这种特定的心肌病中，无论使用何种药物和剂量，我们都未发现功能参数的改善与生存率之间存在任何关联。这个问题指出了至少单独使用交感神经抑制药物预防与阿霉素慢性心脏毒性相关的死亡率的困难。
